We have shown previously that excision of the fundic mucosa results in the withdrawal of an inhibitory mechanism(s) of acid secretion and gastrin release. The aims of this proposal are: (A) to define further this fundic inhibitory mechanism; and (B) to test the hypothesis that vagal inhibition of gastrin release is mediated through the fundus. A. FUNDIC INHIBITORY MECHANISM: Three questions need to be answered. 1) What is the role of the hypergastrinemia after excision of the fundic mucosa of the main stomach, in the development of acid hypersecretion in Heidenhain pouch (HP)? The effect of fundic mucosal excision in previously antrectomized dogs and that of antrectomy in dogs with previous fundic mucosal excision will be studied. 2) Can the hypersecretory state that follows fundic mucosal excision be reversed by the administration of VIP, glucagon and somatostatin, inhibitory peptides already known to exist in the fundic mucosa? 3) Does the parietal cell mass in the HP increase after fundic mucosal excision? Morphometric studies will be employed here. B. ROLE OF THE FUNDUS IN VAGAL INHIBITION OF GASTRIN RELEASE: Two approaches will be employed: 1) Study the effect of truncal vagotomy on gastrin release in dogs with previous fundic mucosal excision. 2) Study of the effect of proximal gastric vagotomy and subsequent truncal vagotomy on gastrin release.